Devices and methods using a pathological frequency in electrical stimulation for pain management

ABSTRACT

An electrical stimulation system includes an implantable control module configured and arranged for implantation in a body of a patient. The implantable control module includes a processor that generates and delivers electrical stimulation pulses or pulse bursts at a pathological frequency or with a temporal separation between pulses or pulse bursts individually selected based on a pre-determined distribution function based on a pre-selected pathological frequency.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. §119(e) of U.S.Provisional Patent Application Ser. No. 62/053,414, filed Sep. 22, 2014,which is incorporated herein by reference.

FIELD

The present invention is directed to the area of implantable electricalstimulation systems and methods of making and using the systems. Thepresent invention is also directed to implantable electrical stimulationsystems that use a pathological frequency to stimulate for painmanagement, as well as methods of making and using the leads andelectrical stimulation systems.

BACKGROUND

Implantable electrical stimulation systems have proven therapeutic in avariety of diseases and disorders. For example, spinal cord stimulationsystems have been used as a therapeutic modality for the treatment ofchronic pain syndromes. Peripheral nerve stimulation has been used totreat chronic pain syndrome and incontinence, with a number of otherapplications under investigation. Functional electrical stimulationsystems have been applied to restore some functionality to paralyzedextremities in spinal cord injury patients.

Stimulators have been developed to provide therapy for a variety oftreatments. A stimulator can include a control module (with a pulsegenerator), one or more leads, and an array of stimulator electrodes oneach lead. The stimulator electrodes are in contact with or near thenerves, muscles, or other tissue to be stimulated. The pulse generatorin the control module generates electrical pulses that are delivered bythe electrodes to body tissue.

BRIEF SUMMARY

One embodiment is a non-transitory computer-readable medium havingprocessor-executable instructions for delivering an electricalstimulation signal, the processor-executable instructions when installedonto a device enable the device to perform actions, including:generating an electrical stimulation signal at a pathological frequencyin a range of 4 to 8 Hz; and delivering the electrical stimulationsignal to one or more selected electrodes of an attached lead.

In at least some embodiments, the electrical stimulation signal includesa series of pulses at the pathological frequency. In at least someembodiments, the electrical stimulation signal includes a series ofbursts at the pathological frequency, where each burst comprises aplurality of pulses within the burst and at a frequency of at least 500Hz. In at least some embodiments, the electrical stimulation signalincludes a base stimulation signal at the pathological frequency and aseries of bursts at the pathological frequency, where each burstincludes a plurality of pulses within the burst and at a frequency of atleast 500 Hz.

In at least some embodiments, the actions further include sensing abiosignal. In at least some embodiments, the actions further includerepeating the generating, delivering, and sensing actions based on ananalysis of the biosignal.

Another embodiment is a non-transitory computer-readable medium havingprocessor-executable instructions for delivering an electricalstimulation signal, the processor-executable instructions when installedonto a device enable the device to perform actions, including:generating electrical stimulation pulses or pulse bursts with a temporalseparation between pulses or pulse bursts individually selected based ona pre-determined distribution function based on a pre-selectedpathological frequency; and delivering the electrical stimulation pulsesor pulse bursts to one or more selected electrodes of an attached lead.

In at least some embodiments, the pre-determined distribution functionis a periodic repeating distribution function. In at least someembodiments, the pre-determined distribution function is a sinedistribution. In at least some embodiments, the pre-determineddistribution function is a normal distribution. In at least someembodiments, the pre-determined distribution function is a distributionfunction that resets with each pulse or burst of pulses.

In at least some embodiments, the actions further include sensing abiosignal. In at least some embodiments, the actions further includerepeating the generating, delivering, and sensing actions based on ananalysis of the biosignal.

Yet another embodiment is an electrical stimulation system that includesan implantable control module configured and arranged for implantationin a body of a patient. The control module is configured and arranged toprovide electrical stimulation signals to an electrical stimulation leadcoupled to the implantable control module for stimulation of patienttissue. The implantable control module includes an antenna configuredand arranged to receive input, and a processor in communication with theantenna and configured and arranged to perform the following actions:generating electrical stimulation pulses or pulse bursts with a temporalseparation between pulses or pulse bursts individually selected based ona pre-determined distribution function based on a pre-selectedpathological frequency; and delivering the electrical stimulation pulsesor pulse bursts to one or more selected electrodes of an attached lead.

In at least some embodiments, the pre-determined distribution functionis a periodic repeating distribution function. In at least someembodiments, the pre-determined distribution function is a sinedistribution. In at least some embodiments, the pre-determineddistribution function is a normal distribution. In at least someembodiments, the pre-determined distribution function is a distributionfunction that resets with each pulse or burst of pulses.

In at least some embodiments, the system further includes a sensor incommunication with the control module, wherein the actions furtherinclude sensing a biosignal using the sensor. In at least someembodiments, the system further includes an electrical stimulation leadcoupleable to the implantable control module and including a pluralityof electrodes disposed along a distal end portion of the electricalstimulation lead.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments of the present invention aredescribed with reference to the following drawings. In the drawings,like reference numerals refer to like parts throughout the variousfigures unless otherwise specified.

For a better understanding of the present invention, reference will bemade to the following Detailed Description, which is to be read inassociation with the accompanying drawings, wherein:

FIG. 1 is a schematic view of one embodiment of an electricalstimulation system that includes a paddle lead electrically coupled to acontrol module, according to the invention;

FIG. 2 is a schematic view of one embodiment of an electricalstimulation system that includes a percutaneous lead electricallycoupled to a control module, according to the invention;

FIG. 3A is a schematic view of one embodiment of the control module ofFIG. 1 configured and arranged to electrically couple to an elongateddevice, according to the invention:

FIG. 3B is a schematic view of one embodiment of a lead extensionconfigured and arranged to electrically couple the elongated device ofFIG. 2 to the control module of FIG. 1, according to the invention;

FIG. 4 is a schematic block diagram of one embodiment of an electricalstimulation system, according to the invention:

FIG. 5A is a graph of one embodiment of stimulation signals in the formof pulses generated and delivered over time, according to the invention;

FIG. 5B is a graph of one embodiment of stimulation signals in the formof bursts of pulses generated and delivered over time, according to theinvention:

FIG. 6A is a graph of one embodiment of stimulation signals in the formof pulses generated and delivered over time based on a periodicrepeating distribution function, according to the invention;

FIG. 6B is a graph of one embodiment of stimulation signals in the formof pulses generated and delivered over time based on a compound periodicrepeating distribution function, according to the invention;

FIG. 6C is a graph of one embodiment of stimulation signals in the formof bursts of pulses generated and delivered over time based on aperiodic repeating distribution function, according to the invention;

FIG. 7 is a graph of one embodiment of stimulation signals in the formof pulses generated and delivered over time based on a distributionfunction that is reset with each pulse, according to the invention;

FIG. 8A is a graph of one embodiment of stimulation signals in the formof continuous portion with pulses generated and delivered over time,according to the invention;

FIG. 8B is a graph of another embodiment of stimulation signals in theform of continuous portion with pulses generated and delivered overtime, according to the invention;

FIG. 9 is a flowchart of one embodiment of a method for generating anddelivering electrical stimulation signals, according to the invention;

FIG. 10 is a flowchart of another embodiment of a method for generatingand delivering electrical stimulation signals, according to theinvention;

FIG. 11 is a flowchart of a further embodiment of a method forgenerating and delivering electrical stimulation signals, according tothe invention; and

FIG. 12 is a flowchart of yet another embodiment of a method forgenerating and delivering electrical stimulation signals, according tothe invention.

DETAILED DESCRIPTION

The present invention is directed to the area of implantable electricalstimulation systems and methods of making and using the systems. Thepresent invention is also directed to implantable electrical stimulationsystems that use a pathological frequency to stimulate for painmanagement, as well as methods of making and using the leads andelectrical stimulation systems.

Suitable implantable electrical stimulation systems include, but are notlimited to, a least one lead with one or more electrodes disposed alonga distal end of the lead and one or more terminals disposed along theone or more proximal ends of the lead. Leads include, for example,percutaneous leads, paddle leads, and cuff leads. Examples of electricalstimulation systems with leads are found in, for example, U.S. Pat. Nos.6,181,969; 6,516,227; 6,609,029; 6,609,032; 6,741,892; 7,949,395;7,244,150; 7,672,734; 7,761,165; 7,974,706; 8,175,710; 8,224,450; and8,364,278; and U.S. Patent Application Publication No. 2007/0150036, allof which are incorporated by reference. It will also be understood thatother electrical stimulation systems can be used including a system thathas an implantable lead coupled to an external control module (such asan external trial stimulator).

FIG. 1 illustrates schematically one embodiment of an electricalstimulation system 100. The electrical stimulation system includes acontrol module (e.g., a stimulator or pulse generator) 102 and a lead103 coupleable to the control module 102. The lead 103 includes a paddlebody 104 and one or more lead bodies 106. In FIG. 1, the lead 103 isshown having two lead bodies 106. It will be understood that the lead103 can include any suitable number of lead bodies including, forexample, one, two, three, four, five, six, seven, eight or more leadbodies 106. An array 133 of electrodes, such as electrode 134, isdisposed on the paddle body 104, and an array of terminals (e.g., 310 inFIG. 3A-3B) is disposed along each of the one or more lead bodies 106.

It will be understood that the electrical stimulation system can includemore, fewer, or different components and can have a variety of differentconfigurations including those configurations disclosed in theelectrical stimulation system references cited herein. For example,instead of a paddle body, the electrodes can be disposed in an array ator near the distal end of a lead body forming a percutaneous lead.

FIG. 2 illustrates schematically another embodiment of the electricalstimulation system 100, where the lead 103 is a percutaneous lead. InFIG. 2, the electrodes 134 are shown disposed along the one or more leadbodies 106. In at least some embodiments, the lead 103 is isodiametricalong a longitudinal length of the lead body 106.

The lead 103 can be coupled to the control module 102 in any suitablemanner. In FIG. 1, the lead 103 is shown coupling directly to thecontrol module 102. In at least some other embodiments, the lead 103couples to the control module 102 via one or more intermediate devices(324 in FIG. 3B). For example, in at least some embodiments one or morelead extensions 324 (see e.g., FIG. 3B) can be disposed between the lead103 and the control module 102 to extend the distance between the lead103 and the control module 102. Other intermediate devices may be usedin addition to, or in lieu of, one or more lead extensions including,for example, a splitter, an adaptor, or the like or combinationsthereof. It will be understood that, in the case where the electricalstimulation system 100 includes multiple elongated devices disposedbetween the lead 103 and the control module 102, the intermediatedevices may be configured into any suitable arrangement.

In FIG. 2, the electrical stimulation system 100 is shown having asplitter 107 configured and arranged for facilitating coupling of thelead 103 to the control module 102. The splitter 107 includes a splitterconnector 108 configured to couple to a proximal end of the lead 103,and one or more splitter tails 109 a and 109 b configured and arrangedto couple to the control module 102 (or another splitter, a leadextension, an adaptor, or the like).

With reference to FIGS. 1 and 2, the control module 102 typicallyincludes a connector housing 112 and a sealed electronics housing 114.An electronic subassembly 110 and an optional power source 120 aredisposed in the electronics housing 114. A control module connector 144is disposed in the connector housing 112. The control module connector144 is configured and arranged to make an electrical connection betweenthe lead 103 and the electronic subassembly 110 of the control module102.

The electrical stimulation system or components of the electricalstimulation system, including the paddle body 104, the one or more ofthe lead bodies 106, and the control module 102, are typically implantedinto the body of a patient. The electrical stimulation system can beused for a variety of applications including, but not limited to deepbrain stimulation, neural stimulation, spinal cord stimulation, musclestimulation, and the like.

The electrodes 134 can be formed using any conductive, biocompatiblematerial. Examples of suitable materials include metals, alloys,conductive polymers, conductive carbon, and the like, as well ascombinations thereof. In at least some embodiments, one or more of theelectrodes 134 are formed from one or more of: platinum, platinumiridium, palladium, palladium rhodium, or titanium.

Any suitable number of electrodes 134 can be disposed on the leadincluding, for example, four, five, six, seven, eight, nine, ten,eleven, twelve, fourteen, sixteen, twenty-four, thirty-two, or moreelectrodes 134. In the case of paddle leads, the electrodes 134 can bedisposed on the paddle body 104 in any suitable arrangement. In FIG. 1,the electrodes 134 are arranged into two columns, where each column haseight electrodes 134.

The electrodes of the paddle body 104 (or one or more lead bodies 106)are typically disposed in, or separated by, a non-conductive,biocompatible material such as, for example, silicone, polyurethane,polyetheretherketone (“PEEK”), epoxy, and the like or combinationsthereof. The one or more lead bodies 106 and, if applicable, the paddlebody 104 may be formed in the desired shape by any process including,for example, molding (including injection molding), casting, and thelike. The non-conductive material typically extends from the distal endsof the one or more lead bodies 106 to the proximal end of each of theone or more lead bodies 106.

In the case of paddle leads, the non-conductive material typicallyextends from the paddle body 104 to the proximal end of each of the oneor more lead bodies 106. Additionally, the non-conductive, biocompatiblematerial of the paddle body 104 and the one or more lead bodies 106 maybe the same or different. Moreover, the paddle body 104 and the one ormore lead bodies 106 may be a unitary structure or can be formed as twoseparate structures that are permanently or detachably coupled together.

Terminals (e.g., 310 in FIGS. 3A-3B) are typically disposed along theproximal end of the one or more lead bodies 106 of the electricalstimulation system 100 (as well as any splitters, lead extensions,adaptors, or the like) for electrical connection to correspondingconnector contacts (e.g., 314 in FIG. 3A). The connector contacts aredisposed in connectors (e.g., 144 in FIGS. 1-3B; and 322 FIG. 3B) which,in turn, are disposed on, for example, the control module 102 (or a leadextension, a splitter, an adaptor, or the like). Electrically conductivewires, cables, or the like (not shown) extend from the terminals to theelectrodes 134. Typically, one or more electrodes 134 are electricallycoupled to each terminal. In at least some embodiments, each terminal isonly connected to one electrode 134.

The electrically conductive wires (“conductors”) may be embedded in thenon-conductive material of the lead body 106 or can be disposed in oneor more lumens (not shown) extending along the lead body 106. In someembodiments, there is an individual lumen for each conductor. In otherembodiments, two or more conductors extend through a lumen. There mayalso be one or more lumens (not shown) that open at, or near, theproximal end of the one or more lead bodies 106, for example, forinserting a stylet to facilitate placement of the one or more leadbodies 106 within a body of a patient. Additionally, there may be one ormore lumens (not shown) that open at, or near, the distal end of the oneor more lead bodies 106, for example, for infusion of drugs ormedication into the site of implantation of the one or more lead bodies106. In at least one embodiment, the one or more lumens are flushedcontinually, or on a regular basis, with saline, epidural fluid, or thelike. In at least some embodiments, the one or more lumens arepermanently or removably sealable at the distal end.

FIG. 3A is a schematic side view of one embodiment of a proximal end ofone or more elongated devices 300 configured and arranged for couplingto one embodiment of the control module connector 144. The one or moreelongated devices may include, for example, one or more of the leadbodies 106 of FIG. 1, one or more intermediate devices (e.g., asplitter, the lead extension 324 of FIG. 3B, an adaptor, or the like orcombinations thereof), or a combination thereof.

The control module connector 144 defines at least one port into which aproximal end of the elongated device 300 can be inserted, as shown bydirectional arrows 312 a and 312 b. In FIG. 3A (and in other figures),the connector housing 112 is shown having two ports 304 a and 304 b. Theconnector housing 112 can define any suitable number of ports including,for example, one, two, three, four, five, six, seven, eight, or moreports.

The control module connector 144 also includes a plurality of connectorcontacts, such as connector contact 314, disposed within each port 304 aand 304 b. When the elongated device 300 is inserted into the ports 304a and 304 b, the connector contacts 314 can be aligned with a pluralityof terminals 310 disposed along the proximal end(s) of the elongateddevice(s) 300 to electrically couple the control module 102 to theelectrodes (134 of FIG. 1) disposed on the paddle body 104 of the lead103. Examples of connectors in control modules are found in, forexample, U.S. Pat. Nos. 7,244,150 and 8,224,450, which are incorporatedby reference.

FIG. 3B is a schematic side view of another embodiment of the electricalstimulation system 100. The electrical stimulation system 100 includes alead extension 324 that is configured and arranged to couple one or moreelongated devices 300 (e.g., one of the lead bodies 106 of FIGS. 1 and2, the splitter 107 of FIG. 2, an adaptor, another lead extension, orthe like or combinations thereof) to the control module 102. In FIG. 3B,the lead extension 324 is shown coupled to a single port 304 defined inthe control module connector 144. Additionally, the lead extension 324is shown configured and arranged to couple to a single elongated device300. In alternate embodiments, the lead extension 324 is configured andarranged to couple to multiple ports 304 defined in the control moduleconnector 144, or to receive multiple elongated devices 300, or both.

A lead extension connector 322 is disposed on the lead extension 324. InFIG. 3B, the lead extension connector 322 is shown disposed at a distalend 326 of the lead extension 324. The lead extension connector 322includes a connector housing 328. The connector housing 328 defines atleast one port 330 into which terminals 310 of the elongated device 300can be inserted, as shown by directional arrow 338. The connectorhousing 328 also includes a plurality of connector contacts, such asconnector contacts 340. When the elongated device 300 is inserted intothe port 330, the connector contacts 340 disposed in the connectorhousing 328 can be aligned with the terminals 310 of the elongateddevice 300 to electrically couple the lead extension 324 to theelectrodes (134 of FIGS. 1 and 2) disposed along the lead (103 in FIGS.1 and 2).

In at least some embodiments, the proximal end of the lead extension 324is similarly configured and arranged as a proximal end of the lead 103(or other elongated device 300). The lead extension 324 may include aplurality of electrically conductive wires (not shown) that electricallycouple the connector contacts 340 to a proximal end 348 of the leadextension 324 that is opposite to the distal end 326. In at least someembodiments, the conductive wires disposed in the lead extension 324 canbe electrically coupled to a plurality of terminals (not shown) disposedalong the proximal end 348 of the lead extension 324. In at least someembodiments, the proximal end 348 of the lead extension 324 isconfigured and arranged for insertion into a connector disposed inanother lead extension (or another intermediate device). In otherembodiments (and as shown in FIG. 3B), the proximal end 348 of the leadextension 324 is configured and arranged for insertion into the controlmodule connector 144.

FIG. 4 is a schematic overview of one embodiment of components of anelectrical stimulation system 400 including an electronic subassembly410 disposed within a control module. It will be understood that theelectrical stimulation system can include more, fewer, or differentcomponents and can have a variety of different configurations includingthose configurations disclosed in the stimulator references citedherein.

Some of the components (for example, a power source 412, an antenna 418,a receiver 402, and a processor 404) of the electrical stimulationsystem can be positioned on one or more circuit boards or similarcarriers within a sealed housing of an implantable pulse generator, ifdesired. Any power source 412 can be used including, for example, abattery such as a primary battery or a rechargeable battery. Examples ofother power sources include super capacitors, nuclear or atomicbatteries, mechanical resonators, infrared collectors, thermally-poweredenergy sources, flexural powered energy sources, bioenergy powersources, fuel cells, bioelectric cells, osmotic pressure pumps, and thelike including the power sources described in U.S. Pat. No. 7,437,193,incorporated herein by reference.

As another alternative, power can be supplied by an external powersource through inductive coupling via the optional antenna 418 or asecondary antenna. The external power source can be in a device that ismounted on the skin of the user or in a unit that is provided near theuser on a permanent or periodic basis.

If the power source 412 is a rechargeable battery, the battery may berecharged using the optional antenna 418, if desired. Power can beprovided to the battery for recharging by inductively coupling thebattery through the antenna to a recharging unit 416 external to theuser. Examples of such arrangements can be found in the referencesidentified above.

In one embodiment, electrical current is emitted by the electrodes 134on the paddle or lead body to stimulate nerve fibers, muscle fibers, orother body tissues near the electrical stimulation system. The processor404 is generally included to control the timing and electricalcharacteristics of the electrical stimulation system. For example, theprocessor 404 can, if desired, control one or more of the timing,frequency, strength, duration, and waveform of the pulses. In addition,the processor 404 can select which electrodes can be used to providestimulation, if desired. In some embodiments, the processor 404 selectswhich electrode(s) are cathodes and which electrode(s) are anodes. Insome embodiments, the processor 404 is used to identify which electrodesprovide the most useful stimulation of the desired tissue.

Any processor can be used and can be as simple as an electronic devicethat, for example, produces pulses at a regular interval or theprocessor can be capable of receiving and interpreting instructions froman external programming unit 408 that, for example, allows modificationof pulse characteristics. In the illustrated embodiment, the processor404 is coupled to a receiver 402 which, in turn, is coupled to theoptional antenna 418. This allows the processor 404 to receiveinstructions from an external source to, for example, direct the pulsecharacteristics and the selection of electrodes, if desired.

In one embodiment, the antenna 418 is capable of receiving signals(e.g., RF signals) from an external telemetry unit 406 which isprogrammed by the programming unit 408. The programming unit 408 can beexternal to, or part of, the telemetry unit 406. The telemetry unit 406can be a device that is worn on the skin of the user or can be carriedby the user and can have a form similar to a pager, cellular phone, orremote control, if desired. As another alternative, the telemetry unit406 may not be worn or carried by the user but may only be available ata home station or at a clinician's office. The programming unit 408 canbe any unit that can provide information to the telemetry unit 406 fortransmission to the electrical stimulation system 400. The programmingunit 408 can be part of the telemetry unit 406 or can provide signals orinformation to the telemetry unit 406 via a wireless or wiredconnection. One example of a suitable programming unit is a computeroperated by the user or clinician to send signals to the telemetry unit406.

The signals sent to the processor 404 via the antenna 418 and thereceiver 402 can be used to modify or otherwise direct the operation ofthe electrical stimulation system. For example, the signals may be usedto modify the pulses of the electrical stimulation system such asmodifying one or more of pulse duration, pulse frequency, pulsewaveform, and pulse strength. The signals may also direct the electricalstimulation system 400 to cease operation, to start operation, to startcharging the battery, or to stop charging the battery. In otherembodiments, the stimulation system does not include the antenna 418 orreceiver 402 and the processor 404 operates as programmed.

Optionally, the electrical stimulation system 400 may include atransmitter (not shown) coupled to the processor 404 and the antenna 418for transmitting signals back to the telemetry unit 406 or another unitcapable of receiving the signals. For example, the electricalstimulation system 400 may transmit signals indicating whether theelectrical stimulation system 400 is operating properly or not orindicating when the battery needs to be charged or the level of chargeremaining in the battery. The processor 404 may also be capable oftransmitting information about the pulse characteristics so that a useror clinician can determine or verify the characteristics.

Methods of communication between devices or components of a system caninclude wired or wireless (e.g., RF, optical, infrared, near fieldcommunication (NFC), Bluetooth™, or the like) communications methods orany combination thereof. By way of further example, communicationmethods can be performed using any type of communication media or anycombination of communication media including, but not limited to, wiredmedia such as twisted pair, coaxial cable, fiber optics, wave guides,and other wired media and wireless media such as acoustic, RF, optical,infrared, NFC. Bluetooth™ and other wireless media. These communicationmedia can be used for communications arrangements in the externalprogramming unit 406 or as antenna 412 or as an alternative orsupplement to antenna 412.

It is known that brain waves and other waves can adopt oscillatorypatterns within a number of different frequency bands. For example,brain wave bands have been detected using EEG and other methods and havebeen designated as, for example, delta, theta, alpha, beta, and gammabands and the like. It at least some instances particular frequencies orfrequency ranges or correlations between them within these bands can beindicative of abnormal conditions. As an example, it has been found thatpain signals can be associated with frequencies in the theta band(approximately 4-8 Hz) that are shifted in frequency (for example,elevated) from a normal, “pain-free” frequency or frequency range withinthat band.

Although not wishing to be bound by any particular theory, it is thoughtthat stimulating neural tissue at or near these characteristicfrequencies or at or near a normal or “pain-free” frequency or frequencyrange can facilitate treatment of pain and, perhaps, shift neuronalactivity to the desired frequency or frequency range or pattern. As anexample, stimulating neural tissue in the spinal cord or elsewhere mayalleviate or reduce pain. In at least some embodiments, a frequency inthe theta band (4-8 Hz) is selected as a desired pathological frequencyand neural tissue is stimulated at or near this pathological frequencyas described in the various embodiments below. Although stimulationusing a frequency in the theta band is described in the embodimentsbelow, it will be understood that other frequencies, including those inbands other than the theta band such as the delta, alpha, beta, or gammabands or at higher or lower frequencies (for example, in the range of 1to 1000 Hz), can also be used for stimulation. In at least someembodiments, stimulating at the selected pathological frequency candisrupt or desynchronize undesirable synchronized neural signals atanother frequency, such as another frequency in the theta band.

The desired stimulation frequency can be selected based on pathologicalinformation. In at least some embodiments, the desired stimulationfrequency can be determined by measurements of biosignals from thepatient. For example, an electroencephalograph (EEG) of the patient canbe used to determine a desired stimulation frequency. The EEG may alsobe used to indicate pathological frequencies or frequency ranges fromthe biosignals that are indicative of pain or other conditions. In otherembodiments, a desired stimulation frequency can be based on aggregateddata from a population of patients. This population may be a generalpopulation or may be selected based on one or more factors such as, butnot limited to, age, gender, race, height, weight, physicalconditioning, existence of a particular medical condition or symptom, orthe like. In yet other embodiments, the desired stimulation frequencymay be selected based on stimulation trials conducted with the patient.In further embodiments, any combination of biosignal measurements,population data, or stimulation trials may be used to aid in selecting astimulation frequency.

Electrical stimulation can be performed at a variety of different siteswithin the patient. For example, the stimulation may be applied at thesite of the pain or other condition or within the brain. In at leastsome embodiments, electrical stimulation is applied to the spinal cord.Examples of spinal cord stimulation systems are described above in thereferences cited above. Stimulation may be performed to any portion ofthe spinal cord including the dorsal columns, dorsal horns, dorsalroots, or any combination thereof. Examples of dorsal root stimulationcan be found at, for example, U.S. Patent Applications Publication Nos.2013/0317583; 2013/0317585; 2013/0317586; 2013/0317587; and2013/0317588, all of which are incorporated by reference. Examples ofdorsal horn stimulation can be found at, for example, U.S. PatentApplication Publication No. 2014/0081349, incorporated herein byreference. In at least some embodiments, electrical stimulation may beperformed at a portion of the spinal cord at or above the region inwhich nerves from the body parts experiencing pain or another conditionfor treatment connect to the spinal cord. In at last some embodiments,the electrical stimulation is applied to provide a parathesia ortingling feeling within the body part to be treated. In at least someembodiments, the electrical stimulation may produce a sub-parathesiaeffect that also provides treatment for pain or other conditions.

The electrical stimulation is produced with at least one electrodeacting as an anode and at least one electrode acting as a cathode. Anyelectrode(s) used to provide the electrical stimulation can be locatedon a lead or microstimulator. In at least some embodiments, an electrodeon the control module can act as an anode or cathode. In the embodimentsdescribed below, the electrical stimulation is characterized as pulsesof relatively steady amplitude current. It will be recognized, however,that other pulse shapes (for example, pulses that ramp up, ramp down, orboth or pulses with steady or varying voltage) can also be used forelectrical stimulation.

FIG. 5A is a graph illustrating one embodiment of a stimulation scheme.In this embodiment, the control module generates pulses 550 at afrequency f₁ that corresponds to a pathological frequency selected asdescribed above. The period T₁ between pulses 550 is 1/f₁. For example,the pathological frequency can be in the theta band of 4 to 8 Hz. It hasalso been found that peripheral stimulation of pain receptors(nociceptive stimulation) causes increased coherence between the thetaband and the gamma band (25 to 90 Hz). Accordingly, stimulation at apathological frequency in the gamma band (25 to 90 Hz) can be effective.

FIG. 5B is a graph illustrating another embodiment of a stimulationscheme in which the control module generates a burst 552 of pulses 554.The bursts occur at a regular frequency f₁ that corresponds to aselected pathological frequency. For example, the pathological frequencycan be in the theta band of 4 to 8 Hz. The period T₁ between pulses 550is I/ft. The pulses 554 within a burst 552 occur at a higher frequencyf₂. In at least some embodiments, the pulses occur at a frequency f₂(with a period T₂=1/f₂) that is in the range of 500 Hz to 5 kHz. Theburst 552 can include any number of pulses 554. In at least someembodiments, a burst includes 2 to 100 pulses or 2 to 20 pulses or 2 to10 pulses.

Although not wishing to be bound by any particular theory, it may bebeneficial to provide electrical stimulation that is not presentedstrictly at a regular frequency, but where there is some variation inthe temporal separation between the pulses or bursts. This is similar tothe body's natural rhythms which are often variable in period andfrequency. Accordingly, a desired stimulation frequency can be selectedwhich represents the average period between pulses and bursts, but theactually delivery of pulses or bursts can be modulated around thiscenter stimulation frequency. FIGS. 6A-7 illustrate embodiments in whichthe temporal separation between pulses or bursts is variable anddetermined based on a distribution function that can be disposed about acenter stimulation frequency or period.

In at least some embodiments, the distribution function that is used todetermine the temporal separation between pulses or bursts is a periodicrepeating distribution function. FIG. 6A is a graph illustrating oneembodiment of a stimulation scheme in which the control module generatespulses 650 where the period T between pulses is variable and is selectedusing a periodic repeating distribution function 656 that has a centerstimulation frequency f₁ (and corresponding center period T₁=1/f₁) thatcan be selected to be a pathological frequency (for example, a thetaband frequency in the range of 4-8 Hz.) The distribution function 656can be normalized for each period and indicates the relative likelihoodthat a given pulse will begin at that time. In the embodimentillustrated in FIG. 6A, the periodic repeating distribution function isa sine wave with a period of T₁. It will be understood that otherdistribution functions can be used include, but are not limited to, anormal distribution, a square wave function, a triangular function, agamma distribution function, and the like. Other examples, such as theembodiment illustrated in FIG. 6B, can include a periodic repeatingcombination distribution function 656 with a distribution section 658such as a sine wave, normal distribution, square wave, or the likeseparated by a flat (for example, zero) distribution section 660. Anyother suitable combination of functions can also be used. Although therepeating function described herein is periodic, in other embodiments,the repeating function may be repeated in an aperiodic manner withvariation in the separation between the repeating functions.Accordingly, any discussion herein regarding the periodic repeatingfunction is also applicable to an aperiodic repeating function.

In at least some of these instances, there can be one or moredistribution variables that may be selectable by a clinician, a patient,or both to define a shape of the distribution. As an example, thestandard deviation of a normal distribution can be a selectable variableor the width of the sine wave 658 and width of the flat distributionsection 660 in the embodiment of FIG. 6B can be selectable variables.The width of a square wave distribution or the width of a triangulardistribution (at its base or at half maximum or any other position alongthe triangle) can also be selectable variables.

FIG. 6C is a graph illustrating another embodiment of a stimulationscheme in which the control module generates a burst 652 of pulses 654where the period T between bursts is variable and is selected using aperiodic repeating distribution function 656 that has a center frequencyf₁ (and corresponding center period T₁=1/f₁) that can be selected to bea pathological frequency (for example, a theta band frequency in therange of 4-8 Hz.) The distribution function 656 can be normalized and isa function of the relative likelihood that a given pulse will begin atthat time. In the embodiment illustrated in FIG. 6C, the periodicrepeating distribution function is a sine wave. It will be understoodthat any of the other distribution functions described with respect tothe embodiments of FIGS. 6A and 6B can also be utilized with a burst 652of pulses 654. The pulses 654 within a burst 652 occur at a higherfrequency f₂. For example, the pulses may occur at a frequency f₂ (witha period T₂=1/f₂) that is in the range of 500 Hz to 5 kHz. The burst 652can include any number of pulses 654. In at least some embodiments, aburst includes 2 to 100 pulses or 2 to 20 pulses or 2 to 10 pulses.

In at least some embodiments, the probability of the next pulse or burstcan depend on the previous pulse(s) or burst(s). FIG. 7 illustrates oneembodiment in which the likelihood of a pulse 750 occurring at a giventime depends on a distribution function 756 (which is partiallyillustrated for each pulse in FIG. 7). In these embodiments, thedistribution function is reset by a triggering occurrence. In theembodiment of FIG. 7, the triggering occurrence can be the end of thepreceding pulse (or even the beginning of the preceding pulse with thedistribution function being zero during the preceding pulse).

FIGS. 8A and 8B illustrate embodiments in which continuous stimulation862 is produced at a frequency f₁ (with a corresponding period T₁) withbursts 864 of pulses 866 during every period (FIG. 8A) or half period(FIG. 8B). For example, the pathological frequency can be in the thetaband of 4 to 8 Hz. The period T₁ is 1/f₁. The pulses 866 within a burst864 occur at a higher frequency f₂. In at least some embodiments, thepulses occur at a frequency f₂ (with a period T₂=1/f₂) that is in therange of 500 Hz to 5 kHz.

In at least some embodiments, the electrical stimulation signal (such asthe signals illustrated in FIGS. 5A-8B) can be provided on a continuousbasis or at regular or irregular intervals which may be programmed intothe control module. In at least some embodiments, the patient may directthe initiation of electrical stimulation using an external device thatis in communication with the control module.

In at least some embodiments, the system may include one or more sensorsor be in communication with one or more sensors that monitor one or morebiosignals. Examples of suitable biosignals include, but are not limitedto, EEG, electrocochleograph (ECOG), heart rate, ECG, blood pressure,electrical signals traversing the spinal cord or a nerve or group ofnerves, and the like. The sensor or control module may analyze thebiosignal(s) and may initiate electrical stimulation, or terminateelectrical stimulation, in response to the biosignal(s). In at leastsome embodiments, the generation and delivery of electrical stimulationsignals can be used in a feedback loop. For example, one or more sensorssense one or more biosignals and the electrical stimulation systemgenerates and delivers electrical stimulation, or terminates thegeneration and delivery of electrical stimulation, based on thebiosignal(s). If a biosignal indicates a particular abnormal or paincondition, the system may begin, or continue, to generate and deliverthe electrical stimulation. The absence of the abnormal or paincondition for a predetermined period of time may cause the system toterminate the generation and delivery of electrical stimulation.

FIG. 9 is a flowchart of one embodiment of a method of electricalstimulation of patient tissue. In step 902, an electrical stimulationsignal at a pathological frequency is generated in, for example, thecontrol module. The electrical stimulation signal can be a series ofpulses (see, for example, FIG. 5A) or a series of bursts of pulses (see,for example, FIG. 5B). In some embodiments, the electrical stimulationsignal can have a continuous portion with pulses or bursts produced atthe pathological frequency (see, for example, FIGS. 8A and 8B.) In step904, the electrical stimulation system is delivered to patient tissueusing one or more electrodes.

FIG. 10 is a flowchart of one embodiment of a method of electricalstimulation of patient tissue. In step 1002, an electrical stimulationsignal is generated in, for example, the control module using a periodicrepeating distribution function. The periodic repeating distributionfunction can be, for example, a sine wave (see, for example, FIGS. 6Aand 6C), a normal distribution, a square wave, a triangular wave, acombination function (see, for example, FIG. 6B which uses a sine waveand a flat zero distribution section), or any other suitabledistribution. The electrical stimulation signal can be a series ofpulses (see, for example, FIGS. 6A and 6B) or a series of bursts ofpulses (see, for example, FIG. 6C). In step 1004, the electricalstimulation system is delivered to patient tissue using one or moreelectrodes.

FIG. 11 is a flowchart of one embodiment of a method of electricalstimulation of patient tissue. In step 1102, an electrical stimulationsignal is generated in, for example, the control module using adistribution function that restarts with each pulse or burst (see, forexample, FIG. 7). The periodic repeating distribution function can be,for example, a sine wave (see, for example, FIG. 7), a normaldistribution, a square wave, a triangular wave, a combination function,or any other suitable distribution. The electrical stimulation signalcan be a series of pulses (see, for example, FIG. 7) or a series ofbursts of pulses. In step 1104, the electrical stimulation system isdelivered to patient tissue using one or more electrodes.

FIG. 12 is a flowchart of one embodiment of a method of electricalstimulation of patient tissue. In step 1202, an electrical stimulationsignal is generated in, for example, the control module. In step 1204,the electrical stimulation system is delivered to patient tissue usingone or more electrodes. These steps can be performed using any of themethods illustrated in FIGS. 9-11 or by any other suitable method.

In step 1206, the effect of the electrical stimulation signal can bedetermined. In at least some embodiments, the effect is determined bymeasuring a biosignal. Examples of suitable biosignals include, but arenot limited to, EEG, electrocochleograph (ECOG), heart rate, ECG, bloodpressure, electrical signals traversing the spinal cord or a nerve orgroup of nerves, and the like. The biosignal may be obtained from asensor that is part of the electrical stimulation system or separatefrom the system. The sensor may communicate with the control moduleusing any wired or wireless communication arrangement. In step 1208, thesystem or a user can decide whether to repeat the procedure to provideadditional electrical stimulation or can decide to terminate thestimulation because, for example, the condition that is to be treated(for example, pain) has been reduced or alleviated as indicated by thebiosignal. If the decision is to repeat, then steps 1202-1206 can berepeated as illustrate in FIG. 12.

This process can be used as a feedback loop to provide electricalstimulation to patient tissue. The feedback loop may be part of aprogramming session. Alternatively or additionally, the electricalstimulation system may initiate the feedback loop on a regular orirregular basis or when requested by a user, clinician, or otherindividual to adjust stimulation parameters.

It will be understood that the system can include one or more of themethods described hereinabove with respect to FIGS. 9-12 in anycombination. The methods, systems, and units described herein may beembodied in many different forms and should not be construed as limitedto the embodiments set forth herein. Accordingly, the methods, systems,and units described herein may take the form of an entirely hardwareembodiment, an entirely software embodiment or an embodiment combiningsoftware and hardware aspects. The methods described herein can beperformed using any type of processor or any combination of processorswhere each processor performs at least part of the process.

It will be understood that each block of the flowchart illustrations,and combinations of blocks in the flowchart illustrations and methodsdisclosed herein, can be implemented by computer program instructions.These program instructions may be provided to a processor to produce amachine, such that the instructions, which execute on the processor,create means for implementing the actions specified in the flowchartblock or blocks or described for the control modules, externalprogramming units, systems and methods disclosed herein. The computerprogram instructions may be executed by a processor to cause a series ofoperational steps to be performed by the processor to produce a computerimplemented process. The computer program instructions may also cause atleast some of the operational steps to be performed in parallel.Moreover, some of the steps may also be performed across more than oneprocessor, such as might arise in a multi-processor computer system. Inaddition, one or more processes may also be performed concurrently withother processes, or even in a different sequence than illustratedwithout departing from the scope or spirit of the invention.

The computer program instructions can be stored on any suitablecomputer-readable medium including, but not limited to, RAM, ROM,EEPROM, flash memory or other memory technology, CD-ROM, digitalversatile disks (“DVD”) or other optical storage, magnetic cassettes,magnetic tape, magnetic disk storage or other magnetic storage devices,or any other medium which can be used to store the desired informationand which can be accessed by a computing device.

The above specification, examples and data provide a description of themanufacture and use of the composition of the invention. Since manyembodiments of the invention can be made without departing from thespirit and scope of the invention, the invention also resides in theclaims hereinafter appended.

What is claimed as new and desired to be protected by Letters Patent ofthe United States is:
 1. A non-transitory computer-readable mediumhaving processor-executable instructions for delivering an electricalstimulation signal, the processor-executable instructions when installedonto a device enable the device to perform actions, comprising:generating an electrical stimulation signal at a pathological frequencyin a range of 4 to 8 Hz; and delivering the electrical stimulationsignal to one or more selected electrodes of an attached lead.
 2. Thenon-transitory computer-readable medium of claim 1, wherein theelectrical stimulation signal comprises a series of pulses at thepathological frequency.
 3. The non-transitory computer-readable mediumof claim 1, wherein the electrical stimulation signal comprises a seriesof bursts at the pathological frequency, wherein each burst comprises aplurality of pulses within the burst and at a frequency of at least 500Hz.
 4. The non-transitory computer-readable medium of claim 1, whereinthe electrical stimulation signal comprises a base stimulation signal atthe pathological frequency and a series of bursts at the pathologicalfrequency, wherein each burst comprises a plurality of pulses within theburst and at a frequency of at least 500 Hz.
 5. The non-transitorycomputer-readable medium of claim 1, wherein the actions furthercomprise sensing a biosignal.
 6. The non-transitory computer-readablemedium of claim 5, wherein the actions further comprise repeating thegenerating, delivering, and sensing actions based on an analysis of thebiosignal.
 7. A non-transitory computer-readable medium havingprocessor-executable instructions for delivering an electricalstimulation signal, the processor-executable instructions when installedonto a device enable the device to perform actions, comprising:generating electrical stimulation pulses or pulse bursts with a temporalseparation between pulses or pulse bursts individually selected based ona pre-determined distribution function based on a pre-selectedpathological frequency; and delivering the electrical stimulation pulsesor pulse bursts to one or more selected electrodes of an attached lead.8. The non-transitory computer-readable medium of claim 7, wherein thepre-determined distribution function is a periodic repeatingdistribution function.
 9. The non-transitory computer-readable medium ofclaim 7, wherein the pre-determined distribution function is a sinedistribution.
 10. The non-transitory computer-readable medium of claim7, wherein the pre-determined distribution function is a normaldistribution.
 11. The non-transitory computer-readable medium of claim7, wherein the pre-determined distribution function is a distributionfunction that resets with each pulse or burst of pulses.
 12. Thenon-transitory computer-readable medium of claim 7, wherein the actionsfurther comprise sensing a biosignal.
 13. The non-transitorycomputer-readable medium of claim 12, wherein the actions furthercomprise repeating the generating, delivering, and sensing actions basedon an analysis of the biosignal.
 14. An electrical stimulation system,comprising: an implantable control module configured and arranged forimplantation in a body of a patient, wherein the control module isconfigured and arranged to provide electrical stimulation signals to anelectrical stimulation lead coupled to the implantable control modulefor stimulation of patient tissue, wherein the implantable controlmodule comprises an antenna configured and arranged to receive input,and a processor in communication with the antenna and configured andarranged to perform the following actions: generating electricalstimulation pulses or pulse bursts with a temporal separation betweenpulses or pulse bursts individually selected based on a pre-determineddistribution function based on a pre-selected pathological frequency;and delivering the electrical stimulation pulses or pulse bursts to oneor more selected electrodes of an attached lead.
 15. The electricalstimulation system of claim 14, wherein the pre-determined distributionfunction is a periodic repeating distribution function.
 16. Theelectrical stimulation system of claim 14, wherein the pre-determineddistribution function is a sine distribution.
 17. The electricalstimulation system of claim 14, wherein the pre-determined distributionfunction is a normal distribution.
 18. The electrical stimulation systemof claim 14, wherein the pre-determined distribution function is adistribution function that resets with each pulse or burst of pulses.19. The electrical stimulation system of claim 14, further comprising asensor in communication with the control module, wherein the actionsfurther comprise sensing a biosignal using the sensor.
 20. Theelectrical stimulation system of claim 14, further comprising theelectrical stimulation lead coupleable to the implantable control moduleand comprising a plurality of electrodes disposed along a distal endportion of the electrical stimulation lead.